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The Disruptive Behavior
Disorders are the most common psychiatric disorder of childhood, with a
prevalence of 4-9% of the entire pediatric population.
The incidence is particularly high in patients with below average IQ,
approximately 3-4 times more common than in children with normal IQ.
There are often comorbid psychiatric diagnoses, including mood disorders,
substance abuse, and ADHD. It is
estimated that approximately two-thirds of children with ADHD will also have a
disruptive behavior disorder diagnosed. The
Disruptive Behavior Disorders can be classified according to DSM-IV into conduct
disorder, oppositional defiant disorder, and disruptive behavior, NOS (18,19).
I. Conduct Disorder --- A repetitive and persistent pattern of behavior in which the basic rights of others or major age-appropriate societal norms or rules are violated, as manifested by the presence of three or more of the following criteria in the past 12 months, with at least one criterion present in the past 6 months:
The disturbance in behavior causes clinically significant impairment in social, academic, or occupational functioning, and criteria is not met for antisocial personality disorder if the patient is 18 years of age.
II. Oppositional Defiant Disorder (ODD) --- A pattern of negativistic, hostile, and defiant behavior lasting at least 6 months, during which four or more of the following are present:
The disturbance in behavior causes clinically significant impairment in social, academic, or
occupational functioning.
The behaviors do not occur exclusively during the course of a Psychotic or Mood Disorder
Criteria are not met for Conduct Disorder or Antisocial Personality Disorder(if older than 18)
III. Disruptive Behavior Disorder, NOS --- This
category is for disorders characterized by conduct or oppositional defiant
behaviors that do not meet the criteria for Conduct Disorder or Oppositional
Defiant Diorder.
I. Lithium carbonate – naturally occurring salt with mood altering properties; FDA approved for the treatment of Bipolar disorder, type I.
à Until 1999-2000, there had been 4 double blind placebo controlled studies done in children to determine the antiaggressive effect of Lithium carbonate in the treatment of conduct disorder. Two trials showed statistically significant benefit, while two did not (10). A larger of theses studies looking at 50 hospitalized children aged 5-12 with aggressive type conduct disorder found 68% improvement in the Lithium group versus 40% improvement in the placebo group. Marked improvement was noted in 40% of patients treated with Lithium versus 4% given placebo (11).
A Double Blind Placebo Controlled Study of Lithium in Hospitalized Aggressive Children and Adolescents With Conduct Disorder (1)
·
Six week study
of patients ages 10-17 admitted to for severe aggression, and diagnosed with
conduct disorder as per DSM-III-R.
·
Randomized,
double-blind, placebo-controlled trial with parallel group design and an initial
2 week single blind placebo period
·
Scales used for
initial evaluation and comparison of groups included Overt Aggression Scale
(OAS), Clinical Global Impressions (CGI), and the Global Clinical Judgements
Consensus Scale (GCJCS)
·
40 patients met
criteria and were included into study, with initial general medical evaluation,
vitals, height, weight, CBC, LFT, TSH, electrolytes, U/A, EKG, and pregnancy
test if applicable
·
20 patients
started on 600mg/d Li2CO3, and increased by 300mg/d to reach blood level
0.8-1.2. 20 patients were kept on
placebo
Outcome
as measured by:
Lithium
Placebo
GCJCS 16/20 improved 6/20 improved
CGI 14/20 improved 4/20 improved
OAS -2.4 from baseline -1.17 from baseline
Adverse effects: Nausea (12 v. 5), vomiting (11 v. 4), and urinary frequency (11 v. 4) occurred more in the treatment group than with placebo. Weight gain was not significantly different than placebo, with 1.9kg (17) vs. 1.6kg (16), respectively. There was one episode on asymptomatic elevation of LFT with lithium and no abnormalities in vital signs.
II. Valproic Acid – FDA approved for partial complex seizures, migraine, and manic episodes
à An earlier open trial of VPA in 10 adolescents with chronic temper outbursts and mood lability showed 100% response to initiation of medication (10).
Divalproex Treatment for Youth with Explosive Temper and Mood Lability: A Double-Blind, Placebo Controlled Crossover Design (2)
Outcome Initial Crossover Adverse effects
Valproic acid 8/10 improved 6/7 improved Increase appetite (20%)
Placebo 0/10 improved 2/8 improved
III. Carbamazepine – FDA approved for partial/complex, generalized, and mixed seizures, as well as trigeminal neuralgia
à Three double blind controlled studies in the early 1970’s with patients exhibiting aggressive behavior showed 71% improvement with carbamazepine versus 26% improvement with placebo. Of note, most of these patients had abnormal EEG’s (10).
Carbamazepine in Aggressive Children with Conduct Disorder: A Double Blind and Placebo Controlled Study (6)
·
Randomized
double blind placebo controlled trial involving 24 children ages 5-12, who were
hospitalized for explosive aggressiveness, and were diagnosed with CD as per
DSM-III.
·
A 2 week
washout period was followed by a 6 week trial of Tegretol 200mg/d divided TID
versus placebo. The Tegretol dose was increased by 200mg to a max of one gram in
order to reach therapeutic blood levels of 4.9 to 9.1ug/mL.
The average dose was 400-800 mg/d
·
Outcome was
measured by OAS, CGI, and CPRS (Children Psychiatric Rating Scale)
·
12 patients
received carbamazepine and completed the study, 11 received placebo
·
There was NO
significant change in any of the hostility or aggression scales above between
carbamazepine and placebo
·
Adverse effects
were common, but not noted if significantly different than placebo: Leukopenia,
transient (6 drug vs. 0 placebo), weight gain of approximately 2 kg (10 vs. 6),
and weight loss (2 vs. 3).
·
Other potential
adverse effects that were noted in this and previous studies include rash,
drowsiness, psychosis, ataxia, diplopia, vertigo, and elevated LFT
IV.
Risperidone – Atypical
antipsychotic used in the management of schizophrenia.
It has also found use in the treatment of Tourette’s syndrome, bipolar
disorder, autism, and aggressive behavior (12).
·
Mechanism of
action; serotonin and dopamine receptor antagonist, binding to 5HT-2 receptors
greater than to D2 receptors.
·
Adverse
effects; sedation or insomnia, weight gain, extrapyramidal symptoms, orthostatic
hypotension, hyperprolactinemia, anticholinergic symptoms, and prolongation of
the QTc
à Two double blind, placebo-controlled trials and one
open labeled trial of risperidone in the treatment of children with disruptive
behavior disorder have been conducted. All
showed significant reductions in aggressive behavior compared to placebo (3).
à A recent open labeled trial of risperidone in
children with ADHD, CD, and ODD via DSM-IV criteria was completed.
Patients were followed for 8 weeks, started on 0.25-0.5 mg of Risperdal,
with an average dose of 1.27mg. 16/20
(80%) patients showed significant improvement as measured by the CGI (5).
à Reports from an ongoing study in England looking at
children with ADHD and ODD or CD note benefit from Risperdal at doses 0.5 to
6mg. These patients were on
stimulants and had usually failed clonidine.
Most common adverse effect was weight gain in 10% of subjects (4).
Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment of Disruptive Behaviors in Children with Subaverage Intelligence (3)
·
118 children
ages 5-12 with DSM-IV Axis I diagnoses of ODD, CD or Disruptive Behavior NOS and
Axis II diagnosis of subaverage intelligence (IQ 36-84)
·
6 week trial
involving 11 centers, patients were assessed by Nissonger Child Behavior Rating
Form, Abberant Behavior Checklist, and CGI
·
Patients were
permitted to continue stimulants through the study.
Prolactin, GH, and routine lab tests were checked at onset and conclusion
of study.
·
Risperdal was
started in 55 patients at a dose of 0.01mg/kg/d for 2 days, then 0.02mg/kg/d to
max of 0.06mg/kg/d. The average
dose was 1.16mg/d. 43 patients
completed the 8 wk trial. 44 of 63
patients started on placebo completed the trial.
Ineffectiveness, noncompliance and adverse effects were the most common
cause for dropout
·
Children
treated with risperidone had significantly improved Nissonger Conduct scores
(9.6 v 4.2) and CGI (77% v 33%).
·
Adverse effects
Risperdal (%)
Placebo (%)
Somnolence
51
10
Headache
29
14
Vomiting
20 6
Dyspepsia
15
6
Weight
gain
15
2
Hyperprolactin
13
2
Increased
appetite
11
6
Rhinitis
11
5
No
increase in serious side effects, cognitive impairments, QTc prolongation, or
extrapyramidal symptoms.
V.
Stimulants, Clonidine, and others
à A double blind study was conducted of 83 children
ages 6-15 years with DSM-III criteria for CD and ADHD, randomized to receive
Methylphenidate or placebo for the 3 year study. MPH was titrated to 60mg/d, with an average dose of 41mg/d
(7).
·
Behavior
scales, as the Conners scale, were completed by teachers, parents, and
psychiatrist throughout the study. The
treatment group showed significant improvement in disruptive behavior, physical
aggression, and problem free behavior. Did
not show improvement in social aggression.
·
Adverse effects
of decreased appetite and insomnia were more common in the treatment group (84%
v 46%)
·
Conclusion of
the study is that impulsivity is a key pathologic abnormality in both ADHD and
CD
à A blinded
study was conducted of 24 children ages 6-16 years with diagnosis of ADHD and
ODD or CD, randomized to receive clonidine, methylphenidate, or combination of
both for the 3 month study (9).
·
Methylphenidate
and clonidine doses were titrated to a maximum dose of 40mg/d (divided BID) and
0.3mg/d (divided TID), respectively.
·
Outcome
measures included a disruptive behavior scale completed by parents and teachers.
All 3 groups showed similar improvements in ODD and CD symptoms.
·
Patients taking
combination had higher incidence of bradycardia than clonidine alone (50% v
25%). There was occasional
lengthening of the PR interval in 7.9% patients taking combination and 4.4%
taking clonidine. One other adverse
effect noted was decreased fine motor activity, more common in the clonidine
group
à An blinded Australian study was conducted on 67 white
children with DSM-IV diagnoses of ADHD and ODD or CD already on a stimulant.
Patients were randomized to receive clonidine syrup or placebo for 6
weeks (8).
·
Clonidine
dosing was started at 0.05mg/d and increased after one week to 0.10mg/d –
0.20mg/d
·
Outcome was
assessed by Conduct and Hyperactive Index Subscales of Conners Behavior
Checklist. Significant improvement
was seen with respect to conduct scores (57% v 21%) and non-significant
improvement was seen when assessing hyperactivity (35% v 17%).
·
Adverse effects
in the treatment group included drowsiness and dizziness.
Surprisingly, improvements in the following were seen in the treatment
group; irritability, crying, anxiety, interest, headaches, and talking with
others.
à Very few
and small studies have looked at antidepressants in the management of disruptive
behavior disorders in children.
·
An open trial of trazadone in children with ODD or CD showed
effectiveness in treating aggressive symptoms (15).
·
A study looking
at the effect of desipramine in children with diagnosis of ADHD and either CD or
ODD. Improvements in attention,
hyperactivity, and aggressive behavior were seen in the group taking desipramine
+ MPH, more so than each drug individually or placebo (16).
·
Serotonergic
receptors, specifically 5-HT 1B/1D, are suggested to be more sensitive in
children with ODD.
à Neurontin is a fairly new medication used as a mood
stabilizer, but has been shown to cause behavioral disinhibition in children.
àLamictal is also a new medication indicated as a mood
stabilizer, but is not recommended for children less than 16 years, secondary to
concerns about a Stevens Johnson rash (14).
à The effects of behavioral modification cannot be
overemphasized as a critical adjuvant in the treatment of children with
Disruptive Behavioral Disorders (13).
References:
1)
Malone, R et al.
A Double-Blind Placebo-Controlled Study of Lithium in Hospitalized
Aggressive Children and Adolescents With Conduct Disorder.
Arch Gen Psychiatry. July
2000; 57(7): 649-54.
2)
Donovan, S. J. et al.
Divalproex Treatment for Youth With Explosive Temper and Mood Lability:
A Double-Blind, Placebo-Controlled Crossover Design. Am J Psychiatry. May
2000; 157(5): 818-820.
3)
Aman, M. G. et al.
Double-Blind, Placebo-Controlled Study of Risperidone for the Treatment
of Disruptive Behaviors in Children With Subaverage Intelligence.
Am J Psychiatry. Aug 2002;
159(8): 1337-1346.
4)
Kewley, Geoffrey.
Risperidone in comorbid ADHD and ODD/CD.
J Am Acad Child Adolesc
Psychiatry. Nov 1999; 38(11): 1327-8.
5)
Sabri Ercan, E. et al.
Risperdone in children and adolescents with conduct disorder:
A single center, open label study. Curr
Ther Research, Clin & Exp. Jan
2003; 64(1): 55-64.
6)
Cueva, J. E., et al.
Carbamazepine in aggressive children with conduct disorder:
A double-blind and placebo-controlled study.
J Am Acad Child Adolesc Psychiatry.
Apr 1996; 35(4): 480-90.
7)
Klein, R. G., et al.
Clinical Efficacy of Methylphenidate in Conduct Disorder With and Without
ADHD. Arch Gen Psychiatry.
Dec 1997; 54(12): 1073-80.
8)
Hazel, Philip and John Stuart.
A Randomized Controlled Trial of Clonidine Added To Psychostimulant
Medication For Hyperactive And Aggressive Children.
J Am Acad Child Adolesc Psychiatry.
Aug 2003; 42(8): 886-94.
9)
Connor, Daniel et al.
A pilot study of methylphenidate, clonidine, or the combination in
Pediatrics. Jan 2000; 39(1):
15-25.
10) Ryan,
N. et al.
Mood Stabilizers in Children and Adolescents. J Am Acad Child Adolesc Psychiatry. May 1999; 38(5): 529-36.
11) Campbell,
Magda et al. Lithium in
hospitalized aggressive children with conduct diorder:
A double-blind an placebo-controlled study.
J Am Acad Child Adolesc Psychiatry.
Apr 1995; 34(4): 445-53.
12) Lexi-Comp.
Risperdone: Pediatric drug
information. UptoDate Online.
2004; 1-8
13) Kolko,
D., Bukstein, O., and Jerome Barron. Methylphenidate
and Behavior Modification in Children With ADHD and Conorbid ODD or CD:
Main and Incremental Effects Across Settings. J Am Acad Child Adolesc Psychiatry. May 1999; 38(5): 578-85.
14) Kowatch,
R. and John Bucci. Mood Stabilizers
and Anticonvulsants. Peds Clinic of
North America. Oct 1998; 45(5):
1173-86.
15) Ghaziuddin,
N. and Norman Alessi. An open trial of trazodone in aggressive children.
J Child Adolesc Psychopharmacology.
Win 1992; 2(4): 291-97.
16) Carlson,
Gabrielle et al. Methylphenidate
and desipramine in hospitalized children with comorbid behavior and mood
disorders: Separate and combined
effects on behavior and mood. J
Child Adolesc Psychopharmacology. Fal
1995; 5(3): 191-204.
17) Heddeke,
S. et al. Serotonergic functioning
in children with oppositional defiant disorder:
a sumatriptan challenge study. Biological
Psychiatry. Feb 2002; 51(4): 319-25.
18) Stead,
L. et al. First Aid for the
Psychiatry Clerkship. New York:
McGraw-Hill, 2002.
19) Lewis,
Melvin. Child and Adolescent
Psychiatry: A comprehensive
textbook. Baltimore:
Williams & Wilkins, 1996.
Medline/PsychInfo search keywords: Disruptive Behavior Disorders (ODD/CD), Mood Stabilizers, and Children. Limit to English and Human studies.
For more see the ODD Homepage or the resources below
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The Child Advocate Therapy in Disruptive Behavior Disorders Page.
Copyright © 2004-2008 The Child Advocate All rights reserved.
Revised: January 20, 2008
.